Abstract 183: Hypertension Increases Toll-Like Receptor 2 (TLR2) and Inflammatory Cytokine Expression in the Corpus Cavernosum From Sprague Dawley Rats
Erectile dysfunction (ED) significantly reduces quality of life and is an early warning of cardiovascular disease. The prevalence of ED is higher among hypertensive compared to normotensive men. Activation of the immune system has been implicated in the development of hypertension; however, the role of the immune system in the development of ED remains unknown. In this study, we hypothesized that TLR2, a key player in innate immunity, is increased leading to an inflammatory response in the corpus cavernosum of hypertensive rats. We induced hypertension in male Sprague Dawley (SD) rats (age 15-weeks) via administration of N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, for 4 weeks in drinking water (500mg/L). Our results showed that the mean systolic blood pressure from L-NAME treated rats was significantly greater (p<0.05) compared to controls (208±33 vs 121±3mmHg). Western blot analysis demonstrated that protein expressions of TLR2, along with its primary intra-cellular signaling protein, myeloid differentiation primary response protein 88 (MyD88), were higher in the corpus cavernosum from L-NAME-treated rats compared to controls (1.691±0.2 vs 1.000±0.1) and (2.177±0.2 vs 1.000±0.3), respectively. Our results also showed that, there is an increase in the phosphorylation of the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) in the corpus cavernosum from L-NAME-treated rats compared to controls (2.038±0.2 vs 1.000±0.2). Additionally, the cavernosal tissue expression levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also increased in the L-NAME-treated group compared to control (2.757±0.4 vs 1.000±0.3). Together, these data suggest that increased activation of TLR2 may initiate an inflammatory response which may lead to corpus cavernosum dysfunction, potentially contributing to ED in a rat model of hypertension induced via nitric oxide synthase inhibition.
- © 2012 by American Heart Association, Inc.